We aimed to understand how COVID-19 impacted LGBTQIA+ adolescents’ and young people’s well-being and to explore self-care strategies developed by them to address such effects. A qualitative investigation was conducted with adolescents and young people including 39 men who have sex with men and transgender women aged 15–22 years in Brazil. Data collection comprised digital-based diaries and semi-structured interviews and occurred during physical distancing measures. We adopted an iterative thematic analysis from an intersectional lens to examine how participants’ multiple social identities—such as gender, sexuality, race, and class—influenced their self-care practices. The process of reflecting on and adapting to COVID-19-related restrictions prompted participants to recognize experiences that impacted their well-being throughout their lives, such as stigma, discrimination, and violence. Social class emerged as the primary factor in social differentiation, rather than race, leading to varied effects of the pandemic on participants’ lives. In their quest for a sense of wholeness, participants became more critical of their relationships, often choosing to end toxic and abusive connections while seeking new sources of social support as a key strategy for protecting their well-being. Transgender participants noted that certain aesthetics within the transgender community could be oppressive rather than emancipatory. Engaging with new social media circles and participating in volunteer work were important forms of community engagement, particularly among Black participants. Future research on the long-term effects of COVID-19 on the well-being of adolescents should prioritize articulating structural drivers of inequality in qualitative health research.